Angiogenesis is deeply concerned with occurrence or pathological processes of various inflammatory diseases (rheumatic diseases, psoriasis, etc.), diabetic retinopathy, tumors, etc. Therefore, it has been considered that inhibition of angiogenesis has a connection with therapy and prophylaxis of these diseases and several research groups have searched for substances capable of inhibiting angiogenesis. For example, mention is made of research works for application of Protamine by Taylor [Taylor, S. et al., Nature, 297, 307 (1982)] and for use of heparin in the presence of cortisone by Folkman et al. [Folkman, J. et al., Science, 221, 719 (1983)]. Furthermore, patent applications have been filed directed to ascorbic acid ether and its related compounds (JP-A-131978/1983) or polysaccharide sulfate DS4152 (JP-A-119500/1988) as compounds showing activity of inhibiting angiogenesis. However, the activities of these compounds are not sufficiently satisfactory, and compounds having more satisfactory activity desired.
Cell-proliferation is a function indispensable for growth and maintenance of living organisms. In higher animals, various tissues or organs have specific proliferation mechanisms which are controlled by various controlling substances. In recent years, numerous capable of substances positively controlling cell-proliferation, i.e., "cell-proliferation factors", have been isolated and purified. In addition, it has been made clear that these factors perform an important role in ontogeny and maintenance of life. On the other hand, there are many reports disclosing that abnormal cell-proliferation, especially when such proliferation is out of the control, is related with various diseases. Examples of such diseases include, tumors and arteriosclerosis.
Further, it has been discovered that various cell-proliferation factors participate in activation of immunocompetent cells, especially lymphocytes. Excess production or excess response of these cell-proliferation factors is considered to be one of the factors of aggravating autoimmune diseases or allergic diseases. Therefore, the use of medicines showing actions of selectively inhibiting cell-proliferation factors, controlling responses and of immunosuppression is considered to provide effective means of prophylaxis to cell-proliferation and therapy of these diseases, and also of suppressing graft rejection in internal organ transplantation.